Use of microfluidic reader device for product authentication

ABSTRACT

A microfluidic device that reads a colloidal mixture and separates the colloids based upon size and shape. and in the case of polymer colloids such as DNA, it reads patterns of markers attached to DNA. The combination of different separated fractions and DNA markers (it mapping) constitutes the physical code.

FIELD OF THE INVENTION

The present invention relates to authentication of physical products andmore specifically to a method for anti-counterfeiting products providingsupply chain verification and point-of-origin tracking and means forarchiving.

DESCRIPTION OF THE PRIOR ART

Embodiments of the invention improve upon previous art in the problem ofproviding secure means of checking the authenticity of a good.Authenticity refers to the physical truth that a particular productoriginated from a given supplier, and the aspects of the product'squality that are desired have been met to the standards expected by thesupplier.

Counterfeit items pose a significant and growing problem withconsumer-packaged goods, especially for established brands.Anti-counterfeiting measures for example, for fluid products, havefocused on secure and traceable packaging or on chemical analysis of astatistical sample of the product.

Among methods used for authentication, some companies have implementedstrategies such as adding high tech labeling, coatings or additives topackages that are difficult to duplicate. Although these measures helpto ensure the integrity of the package, they tend to be costly, andstill can be circumvented by determined counterfeiters. The expenseassociated with chemical analysis of a fluid product, does not allow forcomprehensive verification of every package.

Publication Number WO-2018049272-A1 discloses a method for productauthentication by applying an analyte encode security fluid to asubstrate of the product, obtaining a sample of the fluid from thesubstrate, and testing the sample for the presence of the analyte.

U.S. Pat. No. 6,576,422 discloses an early attempt to identify a productinvolving the steps of: (1) associating with the product a markerligand; and (2) detecting the marker ligand in the product at a laterpoint in time as a means of identifying the product by contacting theproduct with a detector composition.

The detector composition comprises one or more first nucleotidesequences encoding one or more natural or synthetic ligand-dependenttranscription factors, wherein said factors comprise at least one ligandbinding domain, at least one DNA binding domain and at least onetransactivation domain; and a second nucleotide sequence encoding areporter gene under the regulatory control of a receptor responseelement or a modified or synthetic response element, and a secondpromoter.

The disclosed method may also employ a corepressor or coactivator or anucleotide sequence encoding the corepressor, activator Interactionbetween the marker ligand and ligand binding domain is highly specificand induces a change in the expression of the reporter gene, the changeproducing a detectable signal identifying the presence of the markerligand in the product. The detector composition is a cell linecontaining the first and second nucleotide sequences. Kits using themand products marked with specific marker ligands are useful in themethod.

A more recent approach for authenticating a product is described inUnited States Publication Number 20150111780 that relates to anucleic-acid based product authentication by determining authenticationcodes comprising target nucleic-acids using oligonucleotide probesimmobilized on particulate and non-particulate substrates. The presenceof the authentication code is determined using detection methods capableof particle discrimination based on light scattering or fluorescence ofthe particle, or by spatial resolution of oligonucleotides immobilizedat specific loci on a substrate.

Publication Number WO-2014171767-A1 discloses a method for determiningthe authenticity of a honeybee sample by detecting a plant DNA and ahoneybee DNA in the honey sample.

U.S. Pat. Nos. 8,415,164 and 8,415,165 each disclose systems and methodsfor: a.) securing document printing inks, paints pigments within inkcartridges or such items, and b.) authenticating sports garments or IDtags, respectively, in each case, by applying a particular nucleic acidmaterial associated with a particular sequence of nucleic acid bases tothe ink or to the garment; collecting a sample of the ink/garment havingthe nucleic acid; and verifying whether the ink/garment is genuine bydetecting the particular nucleic acid material. The particular nucleicacid material may, in certain embodiments, be deoxyribonucleic acid(DNA).

In other embodiments the particular nucleic acid material may beribonucleic acid (RNA). In certain embodiments the method furthercomprises detecting the particular nucleic acid by performing apolymerase chain reaction (PCR) of the nucleic acid material.

The use of colloidal macromolecules such as DNA as a coding object havebeen previously described. In cases using DNA, its chemical make-up,which allows specific codes to be synthesized and read throughreplication and sequencing, were used to provide a practical means ofproviding authentication. However, the very aspect which allows thesesystems to readily read-out the authentication code (i.e. the DNA basesequence) makes it facile to replicate and counterfeit. There are nodegrees of freedom in changing the code at the time of authentication byphysical means; the code can only be changed at the time of synthesis,and the code can be readily replicated with economical means, allowing alower barrier to entry for counterfeiters.

Another approach to authentication is found in United States PublicationNumber 20170307497-A1 which discloses systems and methods foridentifying fluid-phase products by endowing them with fingerprintscomposed of dispersed colloidal particles, and by reading out thosefingerprints using a Total Holographic Characterization.

Unlike the prior art, embodiments of the present invention include ahigh complexity colloidal mixture comprising spherical particles (e.g.polymer beads, core-shell quantum dots, nanocrystals, etc.) and polymers(e.g. DNA) to provide a highly adaptable “physical encoding” system.

The high complexity colloidal mixtures produce codes that can be readwithin a reasonable time span for authentication, but the codes arephysically challenging to reproduce for counterfeiting with respect tothe point-of-origin user's ability to alter the code. The high complexcolloidal mixtures are read using micro/nanofluidic devices as apoint-of-use check of authentication.

SUMMARY OF THE INVENTION

The embodiments of the present invention describe a structure comprisinga mixture of colloids, which can implanted into a product as a travelingauthentication code.

A method is described in which the colloid mixture is extracted and“read” using another structure which is a microfluidic device. Thismicrofluidic device consists of a set of nanostructured arrays whichseparate the colloids and read their size/marking patterns.

The degree of separation, pattern of markers, and frequency of eventsfor the mixture constitute a unique physical code. This physical code isread and transmitted by the microfluidic device to an authenticationentity which checks the reading results against the accepted value. Asuccessful comparison implies the product is genuine. To combatcounterfeiting, the present invention offers the following advantages:

The system uses a physical code, as opposed to a digital code, reducingthe ability to replicate (i.e. requiring a large amount of time and costto reproduce the constituents of the colloidal mixture).

The system uses microfluidic devices to separate the colloidal mixture,and using the resulting separation pattern as the physical code.

In the system, one is able to alter the separation pattern (the result)by changing the physical conditions under which the colloidal mixture isrun by the microfluidic device. As this change can be specified at thetime of authentication and can be made arbitrary, the ability tocounterfeit (e.g. counterfeiting by generating digital signals thatmimic the result from the microfluidic device) is reduced as it requiresextensive knowledge/empirical data on the behavior of each colloid undera range of physical operating conditions.

Using a set number of colloids, a range of colloidal mixtures (and thuscodes) can be produced using the same method, and using a set number ofcoded polymers, such as DNA, a large number of mapping codes can beproduced using the same method.

A manufacturer can change the code by changing the composition of thecolloidal mixture. This can be done in any time increment, from minutesto years, allowing the ability to rapidly shift the authentication codeagainst possible counterfeiting efforts.

Only small amounts of colloidal mixture are required, allowing thepossibility to embed multiple codes into the product.

The colloidal mixtures can be formulated into inks, paint, or otherelements of the product, providing a way to camouflage them until theyare needed.

The embodiments of the invention described above, disclose a structureand a method, which can be embodied in several different combinations ofdevices and processes. The invention uses a mixture of colloids (10-100nm in diameter) as a physical code which can be implanted into aproduct, and later extracted and read to authenticate the product. Thesecurity of the invention against counterfeit comes from the difficultin time and costs it takes in replicating the colloidal mixture, andthus, the authentication code, versus the time it takes the manufacturerto change the mixture.

The colloidal mixture is read using a microfluidic device whichseparates the colloids based on size and shape, and in the case ofpolymer colloids such as DNA, can read patterns of markers attached tothe DNA. The combination of different separated fractions and DNAmarkers (its mapping) constitutes the physical code.

The physical conditions under which the microfluidic device runs thecolloidal mixture can be changed at the time of authentication, wardingagainst counterfeiting due to the complexity of replicating a largenumber of physical scenarios.

The invention improves the state-of-the-art by using complex microscopicmixtures as a coding medium, providing a means for decoding thesemixtures, and providing a security measure that is adaptable—allowingrapid changing of the authentication code against counterfeiting.

The present invention comprises a computer program product forauthenticating the integrity of a product having a predeterminedphysical code embedded therein, said computer program product comprisinga computer readable storage medium having program instructions embodiedtherewith, said program instructions readable by a microfluidic deviceto cause said microfluidic device to the authenticity of a product andto perform methods defining the authenticity of the product as describedin detail above and hereinafter.

A further embodiment of the present invention, comprises acomputer-implemented method for generating data resulting from passageof a structure (composition) comprising a mixture of colloids as aphysical code through a microfluidic device, which physical code can beimplanted into a product, and later extracted and read to authenticatethe product.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an array schematic and results showing event frequencyfor laterally separated colloids.

FIG. 2 depicts an array schematic for a nano-DLD array and a DNA mappingarray results showing a time translocation variable across the array forthe DNA marker map.

FIG. 3 depicts readout of code results by the use of low flow velocity.

FIG. 4 depicts readout of code results by the use of high flow velocity.

FIG. 5 depicts examples of changing results by changing the colloidformulation concentrations/ratios.

FIG. 6 is a block diagram showing the sequence of steps in theformulation of code and application of same.

FIG. 7 is a schematic of running code in a reader.

FIG. 8 is a schematic representation of nanoscale deterministic lateraldisplacement (nano-DLD) device for reading colloidal solutions.

FIG. 9 is a schematic representation of DNA mapping for reading DNAstrand codes in the formulation.

FIG. 10 is a schematic representation of nanoscale deterministic lateraldisplacement (nano-DLD) device for reading colloidal solutions.

FIGS. 11-13 depict a sequential example of an embodiment of aformulation code being read out by a nano-DLD array.

FIG. 14 is a graph plotting fluorescence intensity (A.U.) as a functionof lateral position (μm) wherein the pattern of peaks is the code fromthe formulation used.

DESCRIPTION OF THE PREFERRED EMBODIMENT

The instant invention is a system for authenticating a product's origin,properties and intended transaction history. The system is devised toreduce the possibility of counterfeiting by providing a high barrier ofentry, both in time and material, to copying the authentication code.

It is intended that the constraints on time/material for counterfeitingthe code (and thus the product) are much greater than the ability of theoriginal producer to change the authentication code, and thus reduce theincentive for duplicity.

A brief summary of an embodiment of the present invention is as follows:a physical authentication code is made from a mixture of small particleswhich can be attached to a product as a traveling security measure.

At any time, a person can verify the authenticity of the product bycollecting the authentication code and running it through a prescribedmicrofluidic device which “reads” the physical code and transmits theresult back, i.e. through wireless communication, to the originalmanufacturer, or an entity maintaining the authentication process.

The science of microfluidics deals with very small volumes of fluids,down to femtoliters (fL) which is a quadrillionth of a liter. Fluidsused in a microfluidic device, i.e., a chip, behave very differently onthe micrometric scale than they do in everyday life.

An authentication code (“code”) consist of a mixture of colloidalparticles, which particles generally are a substance microscopicallydispersed evenly throughout a solution i.e., a solvent. Thedispersed-phase particles can have a diameter between about 5 and 200nanometers.

For the purposes of this invention, the solution composition—comprisinga solvent plus any number of diverse colloids—may also be referred toherein as a “structure”. Practically this is some form of liquidsolution/colloid (fluid) combination, specially formulated, that couldeither be used as-is, or deposited onto a product/packaging, such as anink.

Colloidal particles as found in the present system consist of two types:

1.) Hard-bodied colloidal particles of any variety of shapes (spherical,oblong, rod, branched, prismatic, etc.), sizes, and constructs (singlecrystals, aggregates, self-assembled complexes, etc.). The properties ofshape, size and construction are the major factors for the code mixture.A set of colloids which have a wide span of values for theaforementioned properties is required for producing a code.

Hard-bodied colloidal particles that are suitable for use in the presentinvention are formed using typical nucleation-growth chemistrysynthesis, emulsification and filtration for polymer beads known in theprior art.

The code comprises the types of colloids as mentioned above.

The colloids can constitute: 1.) any particulate matter ranging indiameter from 1-1,000 nm for nanoscale/mesoscale colloidal systems, or1-100 μm for microscale systems.

The colloids can include metal and metal oxide particles, quantum dotsemiconductor particles, organic layer stabilized metal corenanoparticles, polymer particles and microbeads, pigment particles,nucleic acid origami, small molecule aggregates, dsDNA fragments,synthetic polymer fragments, self-assembled protein capsules orcomplexes, deactivated and stabilized cells, pollen, deactivated spores.

The colloids can be of any number of shapes, including spherical,rod-shaped, polyhedral, etc. The colloids can have various propertiessuch as fluorescence, non-linear photo-effects, phosphorescence,elasticity, opto-mechanics, photolysis, photo-aggregation,photo-absorbance, magnetism, etc. The ratio of the diverse colloids inthe formulation which ranges between 0 to 1·10²⁰ particles/mL,preferably between 1·10⁵ and 1·10¹⁴ particles/mL.

2.) Polymeric particles comprising nucleotide-based polymers which canreadily synthesized and encoded with specific base sequences. The DNAbase sequence can be custom selected to allow the attachment of markersto specific, selected sites along the DNA chain.

Nucleotide particles that are suitable for use in the present inventionare preferably DNA, RNA, PNA or any similar polymer created from afamily of double-helical DNA-like polymers where one of the four normalbases is replaced with various cationic, anionic or neutral analogs.

These markers consist of colloidal particles physically or chemicallyattached (bound) to the DNA chain at the selected site(s). Suitablecolloidal marker particles for labeling DNA for mapping includefluorescently labeled cDNA fragments, fluorescently labeled DNAconstructs (specifically, hairpins, origami) with appropriate inserttails, fluorescently labeled binding proteins or complexes,sequence-specific intercalator dyes or pigments.

These marker particles are selected to be compatible with optical orelectrical detection within the microfluidic reader, as described below.The particular sequence of markers along the DNA chain, for a particularchain sequence and chain length, consists of a second tier of physicalencoding. Multiple marker-bound chains can be added to a single code toincrease the complexity depth.

Codes are prepared by mixing different colloids, with differentproperties, in set ratios. The code value consists of the volumefractions of each colloid, and the properties of each colloid, recordedcollectively. A producer, or an entity that produces codes, prepares aunique code by mixing well-defined colloids together and recording thefractions/properties for that code batch.

In addition, additives, including: emulsifiers, anti-coagulants,blockers against non-specific adsorption, anti-photo-bleaching agents,antibiotics, stabilizers, anti-foaming, thickening or thinning agents,salts, pH buffers, sensitizers, and agents for allowing reconstitutionof the formulation into solution can be added to increase the physicalcomplexity of the code.

The code requirements include stability under the conditions of theproduct's transactions, across the lifetime of the product and theability to re-dissolve the code to a reproducible concentration underset conditions. All particles must be charged and have the same chargepolarity (e.g. negative) for electrophoresis (see below).

The code mixture is attached to a product, and travels with the productthrough the lifetime of transaction with the product (e.g. shipment,operation, storage). Attachment can include numerous methodologies:painted on the surface of the product, adsorbed into the product or itspackaging or into a special tag or location on the product, sealed in asmall case or capsule on the surface or inside the product, etc.

The code location can be made conspicuous and concerted, or hidden withthe product/packaging and thus requiring the location of the code to begiven by the authentication entity at the time of authentication.

Multiple codes can be incorporated onto a product, allowing the abilityfor the authentication entity to randomly select a given code for agiven authentication, adding further variability and thus security tothe process. False codes can be made conspicuous while true codes hiddento act as “blinds” against counterfeiters.

The lack of a code on a product constitutes the first security check forauthenticity. The requirement to obtain the location of a hidden codeconstitutes an additional security check.

Embodiments of the present invention utilize microfluidic devices.Microdevices exploit the physical and chemical properties of liquids andgases at the microscale.

A microfluidic chip is a set of micro-channels etched or molded into amaterial (glass, silicon or polymer such as PolyDimethylSiloxane[PDMS]). The micro-channels forming the microfluidic chip are connectedtogether in order to achieve the desired features (mix, pump, sort, orcontrol the biochemical environment).

The microfluidic chip is elaborated so that the incorporated automationallows the user to generate multi-step reactions requiring a low levelof expertise and a lot of functionalities. The microsystems executefunctions that extend from detecting toxins to analyzing DNA sequencesor creating inkjet printing devices.

Microfluidic devices offer several benefits over conventionally sizedsystems. Microfluidics allows the analysis and use of less volume ofsamples, chemicals and reagents reducing the global fees ofapplications.

Many operations can be executed at the same time thanks to microfluidiccompact size, shortening the time of experiment. Microfluidic devicesalso offer an excellent data quality and substantial parameter controlwhich allows process automation while preserving the performances. Theyhave the capacity to both process and analyze samples with minor samplehandling effort on the part of the technician.

This network of microchannels incorporated into the microfluidic chip islinked to the macro-environment by several holes of different dimensionshollowed out through the chip. It is through these pathways that fluidsare injected into and evacuated from the microfluidic chip.

Fluids are directed, mixed, separated or manipulated to attainmultiplexing, automation, and high-throughput systems. The microchannelsnetwork design must be precisely elaborated to achieve the desiredfeatures (lab-on-a-chip, detection of pathogens, electrophoresis, DNAanalysis etc.).

To accurately manage fluids inside the microchannels, specific systemsare required. These elements can either be found embedded inside themicrofluidic chip, such as Quake valves, or outside of it, like in thecase of pressure controllers.

To authenticate a product, the microfluidic reader device describedabove is used. The microfluidic reader consists of: 1. amicro/nanofluidic chip; 2. a fluid for dissolving the code; 3. aninterface for loading fluid into the device/chip; 4. a detector(s)embedded in the chip and/or interfaced to the chip; 5. a housing forprotecting the chip/detector and providing interfacing of fluids to thechip; 6. a driving mechanism for moving fluids/colloids through thechip; 7. a power source; 8. a controller (microcontroller, computer,etc.) for running the chip/detector 9. a wireless transceiver forsending/receiving data; 10. a user interface for operating andmonitoring the authentication process.

The microfluidic reader operates by running the code, dissolved in afluid, through the microfluidic chip and recording the individualcolloids in the code. The recorded output of the code, the “result”, isstored digitally and transmitted to the authentication entity throughthe transceiver.

To prepare the code for the reader, several options are possible; thelocation with the code can be removed and placed in a preset volume offluid to dissolve the constituents, a special tool or applicator withfluid can be used to extract the code directly from the product,capsules, or packets of code can be loaded directly into the readerinterface where their contents are opened and processed. It is requiredthat the fluid (with code) contacts and wets into the microfluidic chip,which primes the chip for reading the code.

The microfluidic chip comprises two components: 1) a nano-DeterministicLateral Displacement (DLD) pillar array (nano-DLD array), 2) a DNAmapping array.

Deterministic lateral displacement (DLD) is a microfluidicparticle-separation technique that makes use of successive bifurcationsof the laminar flow around an array of regularly arranged pillars. Thenano-DLD array uses a microfluidic particle-separation device that makesuse of the asymmetric bifurcation of laminar flow around obstacles. Aparticle chooses its path deterministically on the basis of its size.All particles of a given size follow equivalent migration paths, leadingto high resolution. This technique enables one to separate nanometer tomicrometer-sized particles around a critical diameter called D_(c).Several models are available to anticipate the value of D_(c) accordingto the geometrical characteristics of the DLD array, such as the pillarinter-spacing, the array rotation angle, the shape and the orientationof the pillars. The separation phenomenon is based on steric effectsaround an array of shaped micro-pillars: particles larger than acritical size are laterally displaced by the pillars whereas smallerparticles follow a global straight path.

The nano-DLD array consists of a microchannel into which a lattice ofpillars is fabricated and which is wet with fluid. The lattice isfabricated with an asymmetry which provides the means of separatingparticles laterally across the array according to size and shape in acontinuous flow mode as described in disclosures found in U.S. Pat. Nos.9,636,675 and 10,058,895, the contents of which are hereby incorporatedby reference herein.

The depth, pitch, gap size, pillar shape, pillar diameter, row-shiftoffset and all other geometric parameters of the array can be chosen toselect for a specific separation spectrum of particles according tosize.

In general, for a given array design, particles larger than a criticalsize are displaced laterally within the array at varying angles(depending on the particle size) while particles smaller than thecritical size flow through uninhibited.

The steady-state lateral spatial distribution of a mixture of colloidsof differing shape, size and volume fraction constitutes a physicalencoding of information into a specific, reproducible pattern that canbe observed and recorded. This is the first tier of information storedin the code and which is ascertained by the reader.

FIG. 1 at 100, illustrates a formulation (solution) of colloids ofdifferent sizes being injected into a nano-DLD in a focused jet 101 andhow they displace 102 into a “spectrum” of peaks 103. The degree ofdisplacement (the lateral position) 104 for a given colloid isdetermined by the nano-DLD array's geometry and the geometry and themechanical properties of the colloid itself.

The size and spread of the peaks is determined by the concentration ofthe colloid, diffusion in the array, and the amount of signal receivedfrom each colloid for a given detection method (e.g. scattering,fluorescence, etc.). The accumulated spectrum of peaks 103 at the end ofthe array constitutes a unique pattern that is determined by theformulation and nano-DLD device, and can be used as a physical-basedauthentication code, inherent to the properties of the formulation.

The speed at which colloids are transmitted through the array affectsthe degree of lateral displacement. In addition, hard-bodied sphericalparticles and polymers have anti-correlated responses to flow velocity:at slow flow, polymers such as DNA almost completely displace laterallywhile spherical colloids are diffusion dominated and have no cleardisplacement. At high flow, polymers have little to no displacement,while spherical colloids attain their maximum lateral displacement.

Controlling the flow velocity causes a proportional change in the degreeof lateral displacement of a given colloid, allowing another dimensionof information to be encoded. The basis of affecting polymers (such asDNA) separation based on speed has been described in U.S. Pat. No.9,835,538, the contents of which are hereby incorporated by referenceherein.

FIG. 2 at 200 illustrates a fluorescently backbone-labeled DNAformulation being interrogated by both a nano-DLD array and a DNAmapping array. The nano-DLD emanating from focused jet 201 forms anarray 202 that ultimately forms a spectrum of peaks 203 with each peakdetermined by the length and bound species on the DNA fragment. Each DNAfragment is then fed into a set of nanochannels (mapping array) 204which elongates the DNA into a stretched strand (line) which can be readalong the channels. The length of the fluorescent line indicates thefragment length. The presence of any site-specific fluorescent markersconstitutes a unique pattern 205 that is determined by the formulationand the analysis devices.

The nano-DLD array 202 and DNA mapping arrays 204 do not have to bedirectly coupled as illustrated; they can be run in two separate stages,with the output of the nano-DLD array being read-out first and thenremixed together and fed into the DNA mapping array.

FIGS. 3 & 4 illustrate how fluid velocity can be used as a handle to addadditional complexity to a code formulation. More particularly, FIGS. 3and 4 at 300 and 400 respectively, illustrate the impact that changingthe flow velocity has on the results obtained when authenticating a codethat has been embedded or attached to a product.

FIG. 3 at 300 illustrates a colloid formulation running through anano-DLD array 302 at a low flow velocity 303, showing a particularlateral distribution of colloid peaks 304.

The use of low flow velocity 301 on the various nano-DLD array elements302 results show a lateral positions readout 303 as recorded in theevent frequency bar chart 304. The amplitude of the datum reflected ineach of bars A through E of bar chart 304 reflects the value of eachdatum.

FIG. 4, at 400 by contrast, illustrates the same colloid formulation asthat used in FIG. 3, running at a higher flow velocity 401, which shiftsthe peak distribution 402, showing a particular lateral distribution ofcolloid peaks 403.

The use of high flow velocity 401 on the various nano-DLD array elements402 results show a lateral positions readout 403 as recorded in theevent frequency bar chart 404. The amplitude of the datum reflected ineach of bars A through E of bar chart 404 also reflects the value of thedatum. Bar chart 404 depicts the laterally separated colloid result ofthe code analysis.

The causes for the peak distribution shift have been illustrated in theliterature, and included reduction in the effect of diffusion on thedisplacement process, and shear-induced deformation of the colloidcausing a perturbation in its trajectory through the array. By usingvelocity dependence, a single fluidic code can be expanded into severalfluidic codes by adding the additional parameter of flow velocity, or inaddition, the robustness of an authentication can be increased byrequiring multiple flow velocities to be probed.

To read the lateral displacement of a code mixture in the nano-DLD,optical or electrical methods can be employed. For an optical method,all colloids and DNA markers must emit light (e.g. be fluorescent).

An optical detector, with sufficient spatial temporal intensityresolution, would consist of an excited light source and a photodetectorarray which can be used to line-read the lateral distribution ofcolloids based on the fluorescence intensity. Multiple excitationwavelengths can be used for different fluorescently tagged colloids,allowing another dimension of information encoding. The colloiddistribution can be detected electrically using an array of channelsdownstream of the nano-DLD array to bin the colloid output.

Each channel is built with an electrical detector (e.g. transverseelectrodes, field effect transistor, etc.). The presence of colloids inthe channel is transduced into an electrical signal, and the combinedsignals from each channel are concatenated to describe the distributionof colloids laterally across the nano-DLD array. The lateraldistribution is transcribed into a digital signal, and forms a Tier 1result.

The DNA mapping array consists of a set of nanochannels, running inparallel, which are wet with fluid and which allow colloid particles toflow through the channels. When DNA is flowed into the channels, due tothe size constraints, the polymer must elongate into a linear chain.This unfolding of the coiled state presents the polymer as a linearsequence, with its markers sequentially spaced along its length. Notethere can be two read frames, forward or reverse, depending on which endof the DNA enters the nanochannel first, with respect to the flow.

The specific marker sequence on the elongated DNA chain is termed the“map,” and constitutes a physical encoding of information into aspecific, reproducible pattern that can be observed and recorded. Thisis the second tier of information stored in the code and which isascertained by the reader.

To read the DNA map (“mapping”) of a code mixture in the nano-DLD,optical or electrical methods can be employed.

For an optical method, all DNA markers must emit light (e.g.fluorescent).

An optical detector, with sufficient spatial temporal intensityresolution, would consist of an excited light source and a photodetectorarray which can be used to line read the lateral distribution ofcolloids based on the fluorescence intensity.

The basic technology of DNA mapping with fluorescence has beenpreviously described in patent literature. Multiple excitationwavelengths can be used for different fluorescently tagged markers,allowing another dimension of information encoding. The markerdistribution can be detected electrically using an array of electricaldetectors (e.g. transverse electrodes, field effect transistor, Coultercounter etc.) downstream of the nanochannels to read the linear DNA map.

The presence of DNA, and the presence and sequence of markers along theDNA, in the channel is transduced into an electrical signal as the DNAflows through a nanochannel. The length and spatial distribution ofmarkers along a DNA chain is transcribed into a digital signal, andforms the Tier 2 result.

Note, the DNA can be threaded forward and in-reverse within thenanochannels by reversing the flow to allow multiple-reads of a givenDNA/marker sequence.

The microfluidic chip can be configured to run Tier 1 or combined Tier1+Tier 2 results. For codes consisting of hard-bodied sphericalparticles+DNA, in generally only Tier 1 (i.e. nano-DLD only) results canbe made, as the size range applicable to nano-DLD would clognanochannels necessary for DNA mapping. For codes consisting of onlyDNA, Tier 1+Tier 2 results could be run.

A generic chip consists of an entrance, where the code fluid isintroduced, along with a series of nano-DLD or nano-DLD/DNA mappingarrays. The end of the last array may also consist of capillary pumps oropen holes to allow capillary wetting of the fluid into the device.Alternatively, the chip can be pre-wetted and the interface simply makescontact between the code fluid and the liquid inside the chip.

To run the microfluidic chip and obtain the result, electrophoresis isused.

Electrophoresis, which is one of the electro-kinetic phenomena observedin colloidal systems, is the motion of charged colloidal particles in aliquid medium under an applied electric field. Charged colloidalparticles in the stationary state move with a constant velocity as aresult of the balance between the applied electric field acting on theparticles and a viscous resistance exerted by the liquid on theparticles.

In the case where the magnitude of the applied electric field E is notvery high so that the particle velocity U, which is called theelectrophoretic velocity, is proportional to E in magnitude. The ratioof the magnitude of the velocity U to that of the applied electric fieldE is called the electrophoretic mobility μ, which is defined by μ=U/E(where U=|U| and E=|E|).

In the case of hard particles without surface structures, theelectrophoretic mobility depends on the zeta potential ζ of theparticle. The zeta potential is defined as the potential at the slippingplane, at which the liquid velocity relative to the particle is zero. Ifthe slipping plane is located at the particle surface, the zetapotential ζ becomes equal to the surface potential ψ_(o) of theparticle. In the case where ζ=ψ_(o) and where particles are of sphericalor cylindrical shape, the surface charge density a of a charged particlecan be calculated from the particle surface potential ψ_(o).

In the case of soft particles, that is, e.g., hard particles coveredwith an ion-penetrable surface layer of polyelectrolytes, the concept ofzeta potential loses its meaning and the Donnan potential in the surfacelayer plays an essential role in electrophoresis of soft particles.

Electrodes at the beginning and end of the chip are energized and set upan electric field gradient which drives the migration of the colloidmixture through the arrays. This generates a flow of colloids whichpowers the lateral displacement in the nano-DLD array, and/or theelongation and translocation of DNA through the mapping arrays. Thefield intensity and polarity can be adjusted to affect the speed of flowand direction of flow, respectively. While the colloids are flowingthrough the arrays, the detector observes and records the output as theresult. The result is transmitted digitally to the authenticationentity, which stores the key relating the product to its correct code.

Cross-checking of the transmitted result to the stored correct valueprovides the authentication.

To avoid the ability of a counterfeiter to pre-sample a code and thenartificially construct the result for transmission, different physicalconditions can be arbitrarily chosen and run on the microfluidic device,per the instruction of the authentication service, increasing the numberof possible combinations of results, and reducing the probability of acounterfeit from artificially construction or guessing the correct code.

Physical conditions can include different flow speeds, temperature,viscosity of the fluid, type of fluid, which code is used forauthentication. The necessary hardware for each physical condition canbuild into the chip/reader to allow randomized run states.

The key feature of the invention is the complexity of the code. Toreconstruct the entire code requires the synthesis of colloids withprecise properties, formulated to the correct concentration and theratio of colloids.

FIG. 5 at 500, depicts an example of changing the complexity of the codeby changing formulation concentrations and the ratio of colloids 501.Formulations 502 and 503 each having differe ratio of colloidconstituents, are run as shown in nano-DLD arrays 504 and 505 and resultin different lateral positions 506 and 507. A comparison of eventfrequencies 508 and 509 illustrates the different end result obtainedwhen varying the formulation concentration and the ratio of colloidconstituents. FIG. 5 illustrates how a single pallet of differentcolloids can be used to generate different code formulations.

Five colloids (A, B, C, D and E) 501 of different sizes/shapes are mixedinto two formulations, 1.) 502 and 2.) 503, with different ratios(concentrations) of each colloid. Running each formulation through anano-DLD arrays 504 and 505 leads to the same displacement locations foreach colloid but different peak intensities for each formulation.

The combination of lateral location and peak intensity identifies eachformulation as a unique code. Using this system, a manufacture canmodulate at will the ratios of colloids in a formulation periodicallyover time spans of years, months, weeks, days, hours or shorter, togenerate different codes without expending extra cost on making morecolloid sizes/shapes.

In addition, since the conditions of running the code can be altered atthe time of authentication, a full reconstruction of the code isextremely challenging and requires time and cost. As the code can bearbitrarily formulated rapidly by the source manufacturer, as notedabove, codes can be changed at will.

Thus the time to reconstruct the code by a counterfeiter greatly exceedsthe period over which the code is changed. This provides securityagainst counterfeiting, as the cost and time for mimicking a product istoo high to warrant the investment.

Each code formulation, at the time of production, is recorded and storedfor autheticating against results in the future. Codes can be stored inthe same conditions at those intended for the product. Code results canbe recorded at the time of formulation on standardized readers, and theresults stored digitally for authentication in the future. Code resultsmay need to be processed at the time of receipt at the authenticationentity to resolve the information. This could involve deconvolution oftime series taken for the DNA mapping, cross-correlating lateraldisplacement and mapping data for a given DNA chain.

An algorithm, customized to the particular coding formulation and codetype can be implemented to analyze and compare the transmitted result tothe correct value.

The steps for preparing a formulation for application to a product are:

1. Acquisition or synthesis of requisite colloids, e.g.nucleation-growth chemistry for nanocrystal synthesis, emulsificationand filtration for polymer beads, solid phase synthesis or geneexpression for DNA or RNA followed by bioconjugation of markers.

2. Property analysis of each colloid is conducted to have a clear recordof the colloidal parameters for future authentication. This includes ata minimum, optical properties, identification of colloids, size ofcolloids, length of polymer strands, and their calibrated behavior inthe selected nano-DLD and/or DNA mapping arrays.

3. Identify the complexity of the code as the number of colloids in theformulation directly relates to the density of information, and hencethe difficulty to replicating the code. The number of colloids used willbe a balance of the frequency of having to change the code, theimportance of the goods being protected, the expected sophistication ofany counterfeiting effort against the code, and the economics ofproducing the formulation.

4. The code consists of the types of colloid, the properties of eachcolloids, and the concentration of each colloid in the formulation. Inaddition, the formulation quantity, the type of carrier solvent used,and the need for any additional additives are considered.

5. A list of each colloid component is generated (e.g. by a designer orcomputer). The list can be compiled randomly, or according to analgorithm, or from a pre-compiled set from a list.

The aforementioned list is selected for a particular time, location,and/or product, and represents the contents of the code for thatspecified period.

6. A technician or machine dispenses and mixes the blend to form aformulation.

7. The formulation is aliquoted into any required receptacle (e.g.capsule or pouch) and then transmitted to the required good, or storeduntil time of use. In the case of a direct application of the code (e.g.as a pigment), an ink jet type printer can be used to automaticallyapply the code to the desired location on the product. Additionally, theapplication can be built directly into the printing line for thepackaging or product, to automatically apply the code.

The steps for authentication are: 1. User locates the code on theproduct. In the cases where the code has been hidden, or several codesare present, the user first contacts the authentication entity, which inturn provides information on where the code is located and which is tobe used for that authentication.

2. The user removes the code from the product. This can consist of anynumber of methods, depending on the way the code is applied. If the codehas been directly applied to the product, it may require removing apiece of the product and dissolving the code into a pre-specifiedquantity of fluid. If the code is stored in a pouch or capsule, this canbe directly removed. Special equipment may be specified that improve theaccuracy and reliability of retrieving the code from the packaging.

3. Load the code into the reader. In the case of a seal pouch orcapsule, this may be directly loaded into the reader without furtherhandling steps. In the case of having to reconstitute or re-dissolve thecode, this may involve injection (e.g. by syringe, applicator, pipet,pouring, etc.) into the reader, or into a special cartridge or handerplate which is then inserted into the reader.

4. Reader loads the code into the microfluidic chip. This can be done bycapillary wetting, direct pressurization, electrophoresis, or any othermethod that can impel the colloids in the code fluid into themicrofluidic device.

5. User sets the reader operation. This may involve the user enteringseveral input parameters (e.g. time, date, product, authorizationinformation, etc.), may involve the authorization entity remotelyactivating the reader, or sending information (e.g. authorizationinformation), or an automatic program stored on the reader.

6. The reader checks there is a secure communication line with theauthentication entity, e.g. through encrypted wireless communication.

7. The reader begins the processing. The code fluid/sample is movedthrough the nano-DLD and/or DNA mapping arrays within the fluidic chipand processed. The reader controls the drive force (e.g. electric fieldfor electrophoresis) to maintain the correction operational speed andstability of the code.

8. As each colloid, or as stream of colloids, in the code fluid passesthrough the microfluidic chip, the chip (and any auxiliary electronicsor detectors) read the lateral displacement and mapping information andstore it in the controller.

9. The controller can pre-process stored result information, ifrequired.

10. A code is run until either a sufficient amount of time has passed, asufficient quantity of data has been collected (e.g. number of counts,threshold of counts, resolution accuracy obtained, confidence bandobtained, number of expected results obtained, no unique resultsobserved over a set time span, etc.) or the entire code fluid has beenprocessed.

11. The stored result is then encrypted and transmitted to theauthentication entity.

12. The authentication entity receives the result and checks the datadirectly with the stored, expected value.

13. If there is a discrepancy, the authorization entity may request thecode rerun, or may perform a test of the same code kept in storage, rununder the same conditions.

14. If the code result matches the stored value, the authorizationentity transmits back a positive result, indicating the good or productis authentic.

15. If the code result does not match the stored value, and cannot beverified by further checking, the authorization entity transmits back anegative result, suggesting the good or product is counterfeit or thecode has been tampered with.

FIG. 6 at 600 shows a flow diagram for formulating and applying the codefluid. In a generic protocol, multiple DNA strands (601 (1), 602 (2) and603 (3) . . . ) and their final concentrations in the code fluid areselected and labeled with specific markers. The markers can be anynumber of biological constructs, including small oligomers withfluorescent beads, site-specific binding proteins with fluorophores,etc. The DNA/marker pattern and concentration of each DNA strand lengthis registered.

A set of colloids 601. 602, and 603 of known size, shape,polydispersity, and concentration is selected and their propertiesregistered. The DNA and colloid sets can be mixed to form a finalformulation, or either one used separately for the code fluid. The codefluid mixture can be supplemented with any number of additives toimprove anti-coagulation, non-specific adsorption, photo-bleaching,antibiotics, shelf-life stability, reconstitution from dried state,adhesion, etc. The entire recipe of the formulation is registered as a“master copy” of that formulation.

The code fluid is then applied to the product. The code fluid can beembedded in several ways, including as a small liquid sample in ablister or package, as a dried ink or powder, etc. The product,location, methods, time and date of embedding, and any other pertinentinformation for authentication are registered. The entire accumulationof registered information is then stored as a “master copy” in aprotected sever (or other storage media) which is used to futureauthentication by users afield.

More specifically, the steps of preparing a Tier 2 formulation are shownat 600 in FIG. 6. Synthesized nucleotide-based DNA polymers 601, 602,603 have been encoded with specific based sequences that are customselected. At step 607, markers, consisting of colloidal particles 604,605 and 606 are attached (bound) to specific sites along the DNA chain.At 608, a solution is blended with the DNA that has the particularsequence of markers along its chain, thereby forming the “code.”

An aliquot part of the code (the formulated colloidal mixture) that wasduly prepared is then applied to, or embedded into product 609 to allowits authenticity to be determined later.

Hard bodied colloidal particles of diverse types 604 (A), 605 (B) and606 (C), respectively, embodied within Tier 1, are blended at 608 withsolution, and after the mixture is properly formulated, applied to theproduct.

FIG. 7 at 700, illustrates the manner by which the code is extractedfrom an article using the Reader used in accordance with embodiments ofthe present invention.

For purposes of the present invention, the term “Reader” includes theplurality of elements disclosed above, including loading interface 704,microfluidic chip 705, detector 706, driving mechanism 707, power source708, controller computer 709, user interface 710, and transceiver 711.

Product 701 to be inspected is an entity that has had a specific codeembedded in or attached to it. The embedded or attached code isextracted from product 701 and is formulated to result in a re-dissolvedcolloidal mixture 702 as a code fluid. Code fluid 702 is loaded intoreader 703.

More particularly, FIG. 7 shows a flow diagram of components for theread-out of code fluid. After product 701 is authenticated andinspected, code fluid 702 is extracted by any number of means (puncturedblister, re-dissolved from a conspicuous or hidden ink). The code fluidis then loaded into Reader machine 703.

As noted previously, this can be done by capillary wetting, directpressurization, electrophoresis or any other method that can impel thecolloids in the code fluid into the microfluidic chip. The user sets thereader operation entering input parameters. The reader determines ifthere is a secure encrypted wireless communication with theauthentication entity.

A loading interface 704 accepts code fluid 702 and positions it in afluidic channel for injection into microfluidic chip 705. Fluidic chip705 then reads the lateral displacement and mapping information and thenstores it in controller 709. The results are then checked out with theauthentication entity to confirm the results. Microfluidic chip 705contains the nano-DLD and/or mapping devices which will decipher theconstituents of code fluid 702.

Nano-DLD requires a pressure driven flow, while the DNA mapping requireselectrophoresis. To drive these two flows, driving mechanism 707 locksonto microfluidic chip 705 and positions the necessary pump valves andelectrodes onto the chip for driving pressure and electrophoresis flows,respectively. Once loaded and driven into the microfluidic chip understeady state, the encoding can be read out by scanning the read-outregions of the nano-DLD and mapping devices on detector 706.

Detector 706 generally consists of a light source and detector element(e.g. photodiode or CCD camera). Laser induced fluorescence orscattering is a preferred method for imaging the colloids in thedevices, and multiple detection modalities can be used in the detectorto read out the code fluid.

The interplay of detector 706 and driving mechanism 707 is orchestratedby controller 709 (e.g. microcontroller or micro-computer) whichregulates power supply 708 to the machine and handles the input/ouput atuser interface 710. The user interface can consist of a button grid,touch-screen, computer terminal, etc., which allows the party runningthe authentication process to set-up and monitor the decipheringprocess.

The detector's digital output of the code fluid is sent to controller709, which curates it and transmits it using transceiver 711microfluidic chip 705 (or other mechanism) for analysis andverification. Verification takes place remotely, via a dedicated server(not shown).

The dedicated server compares the submitted information (including theproduct to be authenticated, any time stamp data that is of importanceto the authenticator, and the transmitted read out of the code fluid) tothe stored “master copy” which was generated by the code manufacture atthe time of formulation. A positive match results in a verified messagebeing transmitted back to the reader; a false match results in an errormessage. The reader is encased in a housing to protect its electronicsand sensors, as indicated by box outline within 703.

FIG. 8 at 800 illustrates a top view schematic representation of ananoscale deterministic lateral displacement (nano-DLD) device forreading colloidal solutions.

The device is fabricated onto a silicon substrate 806 using standardnanolithography techniques known in the art. Nano-DLD array 802 consistsof an inlet through silicon via 801 extending to microchannel 803 intowhich has been etched a periodic lattice of pillars 804 (or otherprismatic features) with an angle (glide transition, tilt, etc.) thatdirects the pillar lattice vector at an angle to the channel.

A set of serpentine filters 804, 805 are staged down stream of nano-DLDarray 802 to capture any large particulates that could potentially clogthe array (e.g. microbes, debris, etc.). Inlet 801 and outlet 809 of thearray plumb to through-silicon vias (through-holes not shown) in thesubstrate. The vias allow liquid to be injected into/out of the arrayand facilitate wetting and priming of the device prior to use.

Read area 808 on the device is at the end of nano-DLD array 802, wheremaximum lateral separation has occurred. This location is imaged forread-out of the formulation code. A set of small through-holes, e.g.,alignment hole(s) 810, are set asymmetric into silicon chip 806 to allowproper alignment and securing of the chip into the reader.

FIG. 9 at 900 illustrates a top view of a schematic representation of aDNA mapping device for reading DNA strand codes in the formulation.

The device is fabricated onto a silicon substrate 901 using standardnanolithography techniques known in the art. Mapping device 900 consistsof a series of parallel nanochannels 902 which bridge two microchannelreservoirs where DNA is introduced at injection channel 910.Microchannels at inlet 903 and outlet 904 of the array plumb tothrough-silicon vias 905, 906 (through-holes) in silicon chip substrate901.

Vias 905 and 906 allow liquid to be injected into/out of the array andfacilitate wetting and priming of the device prior to use. The entranceto the nanochannels is fabricated with an elongation region 907, whichcan use any number of standard, known structural features to uncoil andstretch out DNA prior to its loading into the nanochannel. This is aprerequisite for mapping the DNA. Read area 908 can be located at almostany location along the nanochannel 902 route, save for the entrance(depicted at the outlet 906). A set of small through-holes, (e.g.,alignment hole 909), are set asymmetric into silicon chip 901 to allowproper alignment and securing of the chip into the reader 908.

FIG. 10 at 1000, illustrates a top view of a schematic representation ofa device 1000 combining nano-DLD and DNA mapping in sequence to allowmore complicated colloidal formulation reading.

Device 1000 is fabricated onto a silicon substrate 1001 using standardnanolithography techniques. The nano-DLD and mapping sections are thesame as depicted in FIGS. 8 and 9.

The nano-DLD read-out must be performed first, as the colloids caninterfere/clog the nanochannels in mapping section 1010. A microchannel1002 and a transfer channel 1003 link the output of the nano-DLD to theinput of mapping section 1011.

A filter region 1005 is included in transfer channel 1003 to impede allcolloids, of any size/shape, that would clog the nanochannelsdownstream. Two through-silicon vias 1006 and 1007 with electrodes 1008and 1009 respectively in their bore are placed at the beginning and endof transfer channel 1003. The first electrode, transport electrode 1008,is used to electrophoretically drive DNA across transfer channel 1003 tothe area outside the mapping section. This is because the nano-DLDsection uses a pressure drive to operate, but the pressure drop issignificant across the nano-DLD array and cannot be used to drive DNAthrough the mapping nanochannels. Transport electrode 1008 can providethe force to move DNA into position for mapping. The second electrode,e.g., injection electrode 1009, is used to drive the DNA into thenanochannel and move it for reading.

The counter electrode 1009 for the injection process is located in thebore of the outlet through-silicon via. In operation, a potential isapplied between the transport 1007 and injection 1009 electrodes todrive DNA into position by the mapping channels 1010, and then apotential is applied across the injection electrode 1009 and outletthrough-silicon via 1007 to drive DNA into nanochannel 1010 for reading.A set of small through-holes, e.g., alignment holes, 1011 and 1012 areset asymmetric into silicon chip 1001 to allow proper alignment andsecuring of chip 1001 into the reader.

FIGS. 11-13 depict an example of an embodiment of a formulation codebeing read out by a nano-DLD array. FIGS. 11-13 illustrate the resultsof fluorescent images at 470 nm excitation and 510 nm emission, of amixture of YOYO-1 labeled dsDNA fragments (0.1, 1.0 and 10.0 kb) beinginjected into a 200 nm gap nano-DLD array.

In FIG. 11, at an inlet, the DNA formulation is injected as a stream onthe left-hand wall of a microchannel. In FIG. 12, stream processingthrough the array causes the different fragment populations to deflectat different angles, resolving, as shown in FIG. 13 into threeindividual peaks with different peak intensities at the outlet of thenano-DLD array.

FIG. 14 is a graph plotting fluorescence intensity (A.U.) as a functionof lateral position (μm) wherein the fluorescence line profiles at theinlet and outlet, show the resolution of the formulation into threedistinct peaks. The pattern of peaks is the code from this formulation.

As shown in FIGS. 6 and 7, the present invention contemplatesimplementation on a system or systems that provide multi-processor,multi-tasking, multi-process, and/or multi-thread computing, as well asimplementation on systems that provide only single processor, singlethread computing.

Multi-processor computing involves performing computing using more thanone processor. Multi-tasking computing involves performing computingusing more than one operating system task.

A task is an operating system concept that refers to the combination ofa program being executed and bookkeeping information used by theoperating system. Whenever a program is executed, the operating systemcreates a new task for it.

The task is like an envelope for the program in that it identifies theprogram with a task number and attaches other bookkeeping information toit. Many operating systems, including Linux, UNIX®, OS/2®, and Windows®,are capable of running many tasks at the same time and are calledmultitasking operating systems. Multi-tasking is the ability of anoperating system to execute more than one executable at the same time.Each executable is running in its own address space, meaning that theexecutables have no way to share any of their memory. This hasadvantages, because it is impossible for any program to damage theexecution of any of the other programs running on the system. However,the programs have no way to exchange any information except through theoperating system (or by reading files stored on the file system).

Multi-process computing is similar to multi-tasking computing, as theterms task and process are often used interchangeably, although someoperating systems make a distinction between the two.

The present invention may be a system, a method, and/or a computerprogram product at any possible technical detail level of integration.The computer program product may include a computer readable storagemedium (or media) having computer readable program instructions thereonfor causing a processor to carry out aspects of the present invention.

The computer readable storage medium as mentioned above, can be atangible device that can retain and store instructions for use by aninstruction execution device. The computer readable storage medium maybe, for example, but is not limited to electronic storage device, amagnetic storage device, an optical storage device, an electromagneticstorage device, a semiconductor storage device, or any suitablecombination of the foregoing. A non-exhaustive list of more specificexamples of the computer readable storage medium includes the following:a portable computer diskette, a hard disk, a random access memory (RAM),a read-only memory (ROM), an erasable programmable read-only memory(EPROM or Flash memory), a static random access memory (SRAM), aportable compact disc read-only memory (CD-ROM), a digital versatiledisk (DVD), a memory stick, a floppy disk, a mechanically encoded devicesuch as punch-cards or raised structures in a groove having instructionsrecorded thereon, and any suitable combination of the foregoing.

A computer readable storage medium, as used herein, is not to beconstrued as being transitory signals per se, such as radio waves orother freely propagating electromagnetic waves, electromagnetic wavespropagating through a waveguide or other transmission media (e.g., lightpulses passing through a fiber-optic cable), or electrical signalstransmitted through a wire.

Computer readable program instructions described herein can bedownloaded to respective computing/processing devices from a computerreadable storage medium or to an external computer or external storagedevice via a network, for example, the Internet, a local area network, awide area network and/or a wireless network. The network may comprisecopper transmission cables, optical transmission fibers, wirelesstransmission, routers, firewalls, switches, gateway computers, and/oredge servers.

A network adapter card or network interface in each computing/processingdevice receives computer readable program instructions from the networkand forwards the computer readable program instructions for storage in acomputer readable storage medium within the respectivecomputing/processing device.

Computer readable program instructions for carrying out operations ofthe present invention may be assembler instructions,instruction-set-architecture (ISA) instructions, machine instructions,machine dependent instructions, microcode, firmware instructions,state-setting data, configuration data for integrated circuitry, oreither source code or object code written in any combination of one ormore programming languages, including an object oriented programminglanguage such as Smalltalk, C++, or the like, and procedural programminglanguages, such as the “C” programming language or similar programminglanguages. The computer readable program instructions may executeentirely on the user's computer, partly on the user's computer, as astand-alone software package, partly on the user's computer and partlyon a remote computer or entirely on the remote computer or server. Inthe latter scenario, the remote computer may be connected to the user'scomputer through any type of network, including a local area network(LAN) or a wide area network (WAN), or the connection may be made to anexternal computer (for example, through the Internet using an InternetService Provider).

In some embodiments, electronic circuitry including, for example,programmable logic circuitry, field-programmable gate arrays (FPGA), orprogrammable logic arrays (PLA) may execute the computer readableprogram instructions by utilizing state information of the computerreadable program instructions to personalize the electronic circuitry,in order to perform aspects of the present invention.

Aspects of the present invention are described herein and at FIGS. 4 and5, with reference to flowchart illustrations and/or block diagrams ofmethods, apparatus (systems), and computer program products according toembodiments of the invention. It will be understood that each block ofthe flowchart illustrations and/or block diagrams, and combinations ofblocks in the flowchart illustrations and/or block diagrams, can beimplemented by computer readable program instructions.

These computer readable program instructions may be provided to aprocessor of a general-purpose computer, special purpose computer, orother programmable data processing apparatus to produce a machine, suchthat the instructions, which execute via the processor of the computeror other programmable data processing apparatus, create means forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

The aforementioned computer readable program instructions may also bestored in a computer readable storage medium that can direct a computer,a programmable data processing apparatus, and/or other devices tofunction in a particular manner, such that the computer readable storagemedium having instructions stored therein comprises an article ofmanufacture including instructions which implement aspects of thefunction/act specified in the flowchart and/or block diagram block orblocks.

The computer readable program instructions may also be loaded onto acomputer, other programmable data processing apparatus, or other deviceto cause a series of operational steps to be performed on the computer,other programmable apparatus or other device to produce a computerimplemented process, such that the instructions which execute on thecomputer, other programmable apparatus, or other device implement thefunctions/acts specified in the flowchart and/or block diagram block orblocks.

The flowchart and block diagrams in the FIGS. 6 and 7 illustrate thearchitecture functionality, and operation of possible implementations ofsystems, methods, and computer program products according to variousembodiments of the present invention. In this regard, each block in theflowchart or block diagrams may represent a module, segment, or portionof instructions, which comprises one or more executable instructions forimplementing the specified logical function(s). In some alternativeimplementations, the functions noted in the blocks may occur out of theorder noted in the FIGS. 6 and 7.

For example, two blocks shown in succession may, in fact, be executedsubstantially concurrently, or the blocks may sometimes be executed inthe reverse order, depending upon the functionality involved.

It will also be noted that each block of the block diagrams and/orflowchart illustration, and combinations of blocks in the block diagramsand/or flowchart illustration, can be implemented by special purposehardware-based systems that perform the specified functions or acts orcarry out combinations of special purpose hardware and computerinstructions.

Although specific embodiments of the present invention have beendescribed, it will be understood by those of skill in the art that thereare other embodiments that are equivalent to the described embodiments.Accordingly, it is to be understood that the invention is not to belimited by the specific illustrated embodiments, but only by the scopeof the appended claims.

What we claim and desire to protect by Letters Patent is:
 1. Amicrofluidic reader device adapted to authenticate the integrity of aproduct having a physical code embedded therein comprising: amicro/nanofluidic chip adapted to separate colloids based upon size andshape; an interface for loading a fluid containing said physical codethat has been extracted from said product into said chip; a series ofnano-Deterministic Lateral Displacement (DLD) arrays or nano-nucleotidepolymer mapping arrays positioned within said microfluidic chip; atleast one detector embedded in said chip and/or interfaced to said chip;a housing for protecting said chip and providing interfacing of saidfluid to said chip; a driving mechanism for moving said fluid throughsaid chip; a power source; a computer, adapted to operate said chip; awireless transceiver for sending/receiving data; a user interface foroperating and monitoring the authentication process.
 2. The microfluidicreader device defined in claim 1 wherein said microfluidic chipcomprises a set of micro-channels etched or molded into a material, saidmaterial selected from the group consisting of glass, silicon or anorganosilicon compound polymer.
 3. The microfluidic reader devicedefined in claim 2 wherein said organosilicon compound polymer ispolydimethylsiloxane [PDMS] and wherein said micro-channels forming saidmicrofluidic chip are connected together in order to achieve desiredfeatures of mixing, pumping, sorting, and controlling a biochemicalenvironment.
 4. The microfluidic reader defined in claim 3 wherein saidphysical code is an authentication code comprising a mixture of diversecolloidal particles, microscopically dispersed evenly throughout asolvent solution forming a fluid wherein said colloidal particlescomprise: hard-bodied colloidal particles having a variety of physicalshapes, sizes, and constructs; and/or polymeric particles comprisingnucleotide-based polymers adapted to be synthesized and encoded withspecific base sequences.
 5. The microfluidic reader device defined inclaim 4 wherein said micro-nanofluidic chip comprises anano-Deterministic Lateral Displacement (DLD) pillar array componentand/or a (DNA) nucleic acid mapping array component.
 6. The microfluidicreader device defined in claim 5 wherein said (DNA) nucleic acid mappingarray comprise a family of double-helical DNA-like polymers wherein oneof the four normal bases is replaced with various cationic, anionic orneutral analogs.
 7. The microfluidic reader device defined in claim 6wherein said (DNA) nucleic acid mapping array are polymers are selectedfrom the group consisting of deoxyribonucleic acid (DNA), ribonucleicacid (RNA) and peptide nucleic acid (PNA) and wherein saidmicro/nanofluidic chip is adapted to read patterns of markers attachedto said DNA, RNA or PNA.
 8. The microfluidic reader device defined inclaim 5, wherein said microfluidic chip is adapted to separate colloidsforming said physical code based upon the size and shape of saidcolloids to authenticate the integrity of a product having a physicalcode embedded therein.
 9. The microfluidic reader device defined inclaim 8, wherein said micro/nanofluidic chip housing said nano DLD arraycomprises said microchannel wet with fluid into which a lattice ofregularly arranged pillars is fabricated with an asymmetry that providesmeans for separating colloid particles flowing laterally across saidnano DLD array according to size and shape in a continuous flow mode.10. The microfluidic reader device defined in claim 9 wherein said arrayof regularly arranged pillars within said microfluidic chip areconfigured to cause successive bifurcations of laminar flow of saidfluid around said array of regularly arranged pillars that define thedepth, pitch, gap size, pillar shape, pillar diameter, row shift offsetand all other geometric parameters of said array to enable a specificseparation of colloid particles according to size, such that for a givenarray design, colloid particles that are larger than a critical size aredisplaced laterally within said array at various angles, while colloidparticles smaller than the critical size flow through said microchanneluninhibited.
 11. The microfluidic reader device defined in claim 10wherein a steady-state lateral spatial distribution of a mixture ofcolloids of differing shape, size and volume fraction constitutes aphysical encoding of information into a specific, reproducible patternwhich is a first tier of information stored in said physical code andwhich is ascertained by a reader.
 12. The microfluidic reader devicedefined in claim 11 wherein the presence of said colloids in each saidchannel is transduced into an electrical signal, and the combinedsignals from each channel are concatenated to describe the resultingdistribution of colloids laterally across said nano-DLD array, such thatthe resulting lateral distribution is transcribed into a digital signal,and forms a Tier 1 result.
 13. The microfluidic reader device defined inclaim 7, wherein said microfluidic chip contains within said (DNA)mapping array, a set of parallel-running wetted nano-channels allowingcolloid particles to pass therethrough.
 14. The microfluidic readerdevice defined in claim 13, wherein said nano-channels in saidmicro/nanofluidic chip are configured to have size constraints thatrestrict the flow of said (DNA) mapping array, and as a result of sizeconstraints of said nano-channels, said DNA polymer in a folded andcoiled state in said DNA mapping array elongates into a linear chain,presenting said DNA polymer as a linear sequence with markerssequentially spaced along its length.
 15. The microfluidic reader devicedefined in claim 14, wherein the presence of an elongated DNA polymerchain, and the presence of a specific sequence of markers along saidelongated DNA polymer chain in said nano-channel channel is transducedinto an electrical signal as said elongated DNA polymer chain flowsthrough said nano-channel resulting in a said markers along said DNAchain that is transcribed into a digital signal, and forms a Tier 2result.
 16. The microfluidic reader device defined in claim 15, whereina length and a spatial distribution of markers forming a specific markersequence on said elongated DNA chain is a map and constitutes a physicalencoding of information into a specific, reproducible pattern that canbe observed and recorded as Tier 2 information stored in said physicalcode ascertained by a reader.
 17. The microfluidic reader device definedin claim 16, wherein in DNA mapping, there are two possible read frames,forward or reverse of said DNA polymer chain having markers sequentiallyspaced along its length, which are a function on which end of said DNApolymer enters said nano-channel first with respect to the flow.
 18. Themicrofluidic reader device defined in claim 5 further comprising opticalor electrical detectors configured to read lateral displacement of aphysical code mixture in the nanoDLD, or to read a DNA mapping.
 19. Themicrofluidic reader device defined in claim 18 wherein said opticaldetector is configured to read lateral displacement of a physical codemixture in said nano-DLD, said optical detector, having sufficientspatial temporal intensity resolution, including an excited light sourceand a photodetector array used to line-read lateral distribution oflight emitting colloids based on their fluorescence intensity.
 20. Themicrofluidic reader device defined in claim 19 wherein multipleexcitation wavelengths are used for different fluorescently taggedcolloids.
 21. The microfluidic reader device defined in claim 20,wherein said colloid distribution is detected electrically usingtransverse electrodes or a field effect transistor in an array ofchannels downstream of said nano-DLD array, wherein the presence ofcolloids in said channel is transduced into an electrical signal, andthe combined signals from each said channel are concatenated to describethe distribution of colloids laterally across the nano-DLD array. 22.The microfluidic reader device defined in claim 18 further comprising anoptical detector wherein DNA mapping of a code mixture is employed. 23.The microfluidic reader device defined in claim 22 wherein said DNAmarkers emit light.
 24. The microfluidic reader device defined in claim23 wherein said optical detector with sufficient spatial temporalintensity resolution, comprises an excited light source emittingmultiple excitation wavelengths for different fluorescently taggedcolloids and a photodetector array used to line read lateraldistribution of colloids based on fluorescence.
 25. The microfluidicreader device defined in claim 23 wherein multiple excitationwavelengths are used for different fluorescently tagged markers.
 26. Themicrofluidic reader device defined in claim 4 includes a Quaker valveembedded therein to manage fluids flowing inside microchannels in saidmicrofluidic chip.
 27. The microfluidic reader device defined in claim4, wherein said diverse colloids comprising said code have diametersmeasuring 10-100 nm in said solvent solution.
 28. The microfluidicreader device defined in claim 4, to run said microfluidic chip,electrophoresis is used.
 29. The microfluidic reader device defined inclaim 4, wherein electrodes at a beginning and at an end of saidmicrofluidic chip are energized setting up an electric field gradientdriving a migration flow of said colloids, thereby powering lateraldisplacement in said nano-DLD array, and/or elongation and translocationof DNA through the mapping array.
 30. The microfluidic reader devicedefined in claim 5, wherein said microfluidic chip is configured to runTier 1 or combined Tier 1 and Tier 2 results.
 31. A computer program forauthentication of a product having a predetermined code embeddedtherein, said computer program product comprising a non-transitorycomputer readable storage program having instructions embodiedtherewith, said program instructions executable by said computer toperform a method using a microfluidic reader device to authenticate theintegrity of said product having a physical code embedded thereincomprising: in a micro/nanofluidic chip adapted to separate colloidsbased upon size and shape; said chip having an interface loading a fluidcontaining said physical code that has been extracted from said productinto said chip; a series of nano-Deterministic Lateral Displacement(DLD) arrays or DNA nano-nucleotide polymer mapping arrays positionedwithin said microfluidic chip; at least one detector embedded in saidchip and/or interfaced to said chip; a housing for protecting said chipand providing interfacing of said fluid to said chip; a drivingmechanism moving said fluid through said chip; a power source; acomputer operating said chip; a wireless transceiver sending/receivingdata; a user interface for operating and monitoring the authenticationprocess; wherein said microfluidic chip comprises a set ofmicro-channels etched or molded into a material, said material selectedfrom the group consisting of glass, silicon or an organosilicon compoundpolymer; and wherein said physical code is an authentication codecomprising a mixture of diverse colloidal particles, microscopicallydispersed evenly throughout a solvent solution forming a fluid whereinsaid colloidal particles comprise: hard-bodied colloidal particleshaving a variety of physical shapes, sizes, and constructs; and/orpolymeric particles comprising nucleotide-based polymers adapted to besynthesized and encoded with specific base sequences;